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A review of genetic factors contributing to the etiopathogenesis of anorectal malformations

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Abstract

Background

Anorectal malformation (ARM) is a common congenital anomaly with a wide clinical spectrum. Recently, many genetic and molecular studies have been conducted worldwide highlighting the contribution of genetic factors in its etiology. We summarize the current literature on such genetic factors.

Materials and methods

Literature search was done using different combinations of terms related to genetics in anorectal malformations. From 2012 to June 2017, articles published in the English literature and studies conducted on human population were included.

Observations and results

A paradigm shift was observed from the earlier studies concentrating on genetic aberrations in specific pathways to genome wide arrays exploring single nucleotide polymorphisms (SNPs) and copy number variations (CNVs) in ARM patients. Rare CNVs (including 79 genes) and SNPs have been found to genetically contribute to ARM. Out of disrupted 79 genes one such putative gene is DKK4. Down regulation of CDX-1 gene has also been implicated in isolated ARM patients. In syndromic ARM de novo microdeletion at 17q12 and a few others have been identified.

Conclusion

Major genetic aberrations proposed in the pathogenesis of ARM affect members of the Wnt, Hox (homebox) genes, Sonic hedgehog (Shh) and Gli2, Bmp4, Fgf and CDX1 signalling pathways; probable targets of future molecular gene therapy.

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Abbreviations

ARM:

Anorectal malformation

AIP:

Anterior Intestinal portal

CIP:

Caudal Intestinal portal

CNV:

Copy number variation

SNP:

Single nucleotide polymorphism

Shh:

Sonic hedgehog

HOX:

Homebox

AD:

Autosomal dominant

AR:

Autosomal recessive

CS:

Currarino syndrome

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Authors and Affiliations

  1. Department of Pediatric Surgery, All India Institute of Medical Sciences, New Delhi, 110029, India

    Kashish Khanna, Shilpa Sharma & D. K. Gupta

  2. Center for Research and Development, Angeles University Foundation, 2009, Angeles, Philippines

    Noel Pabalan

  3. Molecular Biology Unit, Center for Advance Research, King George’s Medical University, Lucknow, Uttar Pradesh, 226 003, India

    Neetu Singh

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  1. Kashish Khanna
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Correspondence to Kashish Khanna.

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Khanna, K., Sharma, S., Pabalan, N. et al. A review of genetic factors contributing to the etiopathogenesis of anorectal malformations. Pediatr Surg Int 34, 9–20 (2018). https://doi.org/10.1007/s00383-017-4204-2

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